The projects described in this renewal application fall into general areas and are based in large measure on data regarding the immunochemical properties of retinal S-antigen and the characteristics of the S-antigen-specific T cell lines prepared and analyzed during the first two years of the project. I. IMMUNOCHEMISTRY OF S-ANTIGEN. a. Further delineate the uveitogenic epitope in peptide CB123 and continue the search for other epitopes recognized by T cells and antibodies, concentrating on the T cells. b. Continue the localization of the remaining peptides which have not been assigned in the overall structure by determining their N-terminal sequence for alignment in DNA-predicted sequences. c. Examine other peptides since evidence from studies with human S-antigen and a human S-antigen-specific T cell line indicates that another uveitogenic determinant may be present elswhere in S-antigen. II. ANTIGEN-SPECIFIC MODULATION OF THE IMMUNE RESPONSES IN EXPERIMENTAL AUTOIMMUNE UVEORETINITIS (EAU). a. We have evidence that an antibody raised in syngeneic rats to irradiated S-antigen-specific cell lines induces a proliferative response in those line cells in vitro, but not in a PPD-specific line suggesting the presence of antibody recognizing T cell receptor idiotype. Such a reagent could be very useful in vivo where it would specifically bind those cells. Such binding could alter the behavior, viability, migratory patterns or ability of those cells to interact with other elements of the immune system and could provide a therapeutically usefuls system for controlling autoimmunity. Antibodies to the T helper markers have been shown to non- specifically suppress autoimmunity in other systems; presumably the use of a more specific antibody would suppress only the desired response. b. Since anti-idiotypic antibodies raised to antigen-specific antibodies have been shown to also bind the T cell receptor for that antigen, we will test a group of anti-idiotypes raised to anti-S-antigen monoclonal antibodies for such activity. c. Peptides and peptide analogues. An analogue of the peptide which contains the T cell epitope but does not contain the agretope may inhibit antigen activation of the T cell receptor.